Cystic fibrosis (CF) exhibits reduced Cl.sup.- secretion by airway epithelia. Consequently, one of the most debilitating effects of CF is the development of a dehydrated, viscous mucus which obstructs the airways and compromises lung function. Extracellular nucleotide triphosphates, such as ATP or UTP, are able to regulate Cl.sup.- secretion in human airway epithelia and, in combination with an inhibitor of Na.sup.+ transport, may provide an alternative, non-CFTR-dependent mechanism to induce fluid secretion in CF airway epithelia. Extracellular nucleotides also stimulate mucus secretion by goblet cells in vitro and excessive activation of this pathway in vivo may be partly responsible for the hypersecretion observed in chronic bronchitis. In both cases, the responses are mediated by 5'-nucleotide (P.sub.2U) receptors on the cell surface.
Recently, a cDNA encoding a murine ATP/UTP receptor was cloned from neuroblastoma cells by functional expression in Xenopus oocytes (K. Lustig et al., Proc. Natl. Acad. Sci. U.S.A. 90, 5113 (1993)). The receptor, a member of the G protein-coupled receptor superfamily, is activated by UTP and ATP, initiates elevation of cytoplasmic calcium, and has been identified with the subtype of P.sub.2 -receptor provisionally designated P2U. Its pharmacological and signaling properties are very similar to those described for a 5'-nucleotide (P.sub.2U) receptor present in the human airway epithelial cell line, CF/T43, which was derived from a donor with CF (A. Brown et al., Mol. Pharmacol. 40, 648 (1991)).
Isolation and molecular characterization of the receptor for extracellular nucleotides present in human airway epithelia will permit studies of the expression of this receptor in normal and diseased tissues and facilitate identification of new drugs for therapy.